Protoporphyrin IX-mediated sonodynamic therapy promotes autophagy in vascular smooth muscle cells

Li, Qingsong; Kang, Jian; Xiong, Xiaozhen; Liu, Yan; Cao, Wenwu; Liu, Ying; Li, Yongning

doi:10.3892/ol.2017.6394

Cited by 9 publications

(5 citation statements)

References 32 publications

(33 reference statements)

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“…Previous studies have reported that different ultrasonic intensities combined with diverse sound-sensitive agents produce distinct biological effects on specialized cells and tissues [26][27][28]. In this study, we demonstrated that when DVDMS was used in conjunction with ultrasound (diameter: 3.5 cm; resonance frequency: 0.5 MHz; duty factor: 10%; repetition frequency: 100 Hz) on the SCLC H446 cell line, apoptosis was observed.…”

Section: Discussionmentioning

confidence: 57%

Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Inhibits RIP3 Expression and Induces Apoptosis in the H446 Small Cell Lung Cancer Cell Line

Shen

Cao

Sun

et al. 2018

Cell Physiol Biochem

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Background/Aims: Sonodynamic therapy (SDT) is expected to be a new method to solve the clinical problems caused by advanced metastasis in patients with lung cancer. The use of ultrasound has the advantage of being noninvasive, with deep-penetration properties. This study explored the anti-tumor effect of SDT with a new sonosensitizer, sinoporphyrin sodium (DVDMS), on the human small cell lung cancer H446 cell line in vitro and in vivo. Methods: Absorption of DVDMS was detected by a fluorescence spectrophotometer, and DVDMS toxicity was determined using a Cell Counting Kit-8. Mitochondrial membrane potential (MMP) was assessed using the JC-1 fluorescent probe. Cell apoptosis was measured by flow cytometry, and apoptosis-related proteins were detected by western blotting. The expression of cytokines was measured using an enzyme-linked immunosorbent assay and quantitative real-time PCR. To verify the in vitro results, we detected tumor volumes and weight changes in a xenograft nude mouse model after DVDMS-SDT. Hematoxylin and eosin staining was used to observe changes to the tumor, heart, liver, spleen, lung, and kidney of the mice, and immunohistochemistry was used to examine changes in the expression of tumor CD34 and receptor-interacting protein kinase-3 (RIP3), while terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling was used to observe apoptosis in tumor tissues. Results: DVDMS-SDT-treated H446 cells increased the rate of cellular apoptosis and the levels of reactive oxygen species (ROS), cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and caspase-10, and decreased the levels of MMP, RIP3, B-cell lymphoma 2, vascular endothelial growth factor, and tumor necrosis factor-α. The sonotoxic effect was mediated by ROS and was reduced by a ROS scavenger (N-acetyl-L-cysteine). In the in vivo mouse xenograft model, DVDMS-SDT showed efficient anti-cancer effects with no visible side effects. Conclusion: DVDMS-SDT induced apoptosis in H446 cells, in part by targeting mitochondria through the mitochondria-mediated apoptosis signaling pathway, and the extrinsic apoptosis pathway was also shown to be involved. Both apoptosis and changes in RIP3 expression were closely related to the generation of ROS. DVDMS-SDT will be advantageous for the management of small cell lung cancer due to its noninvasive characteristics.

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Section: Discussionmentioning

confidence: 57%

Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Inhibits RIP3 Expression and Induces Apoptosis in the H446 Small Cell Lung Cancer Cell Line

Shen

Cao

Sun

et al. 2018

Cell Physiol Biochem

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“…However, the effect was suppressed when the cell uptake of the particles was blocked by co-incubation with excess free folate (Brazzale et al, 2016). It is also reported that ROS generated by SDT is related to autophagy (Li et al, 2017; Kou et al, 2017). These findings indicates the possibility of a late-phase effect of ROS after TP-HIFU irradiation, warranting further experiments.…”

Section: Discussionmentioning

confidence: 97%

Function of Epirubicin-Conjugated Polymeric Micelles in Sonodynamic Therapy

et al. 2019

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The combinatory use of high-intensity focused ultrasound (HIFU) and epirubicin (EPI)-conjugated polymeric micellar nanoparticles (NC-6300) is thought to be a less invasive and more efficient method of cancer therapy. To investigate the mechanism underlying the combination effect, we examined the effect of trigger-pulsed HIFU (TP-HIFU) and NC-6300 from the perspective of reactive oxygen species (ROS) generation, which is considered the primary function of sonodynamic therapy (SDT), and changes in drug characteristics. TP-HIFU is an effective sequence for generating hydroxyl radicals to kill cancer cells. EPI was susceptible to degradation by TP-HIFU through the production of hydroxyl radicals. In contrast, EPI degradation of NC-6300 was suppressed by the hydrophilic shell of the micelles. NC-6300 also exhibited a sonosensitizer function, which promoted the generation of superoxide anions by TP-HIFU irradiation. The amount of ROS produced by TP-HIFU reached a level that caused structural changes to the cellular membrane. In conclusion, drug-conjugated micellar nanoparticles are more desirable for SDT because of accelerated ROS production and drug protection from ROS. Furthermore, a combination of NC-6300 and TP-HIFU is useful for minimally invasive cancer therapy with cooperative effects of HIFU-derived features, antitumor activity of EPI, and increased ROS generation to cause damage to cancer cells.

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“…This nanocomplex has the capability to release CO 2 bubbles and trigger ultrasound-triggered inertial cavitation (UIC), which directly endorses ROS after the introduction of single injection stimulated by US. After experimentation, in vitro and in vivo results displayed the huge production of ROS, which increased tumor immunogenicity by promoting DC maturation that in return activated CD8 + T cells and inhibited tumors. , …”

Section: Enhancing Cancer Immunotherapy Through Ultrasoundmentioning

confidence: 99%

“…After experimentation, in vitro and in vivo results displayed the huge production of ROS, which increased tumor immunoge-nicity by promoting DC maturation that in return activated CD8 + T cells and inhibited tumors. 238,239 3.5.1. Mechanisms of Immune Activation through ROS.…”

Section: Enhancing Cancer Immunotherapymentioning

confidence: 99%

Enhancing Cancer Immunotherapeutic Efficacy with Sonotheranostic Strategies

et al. 2021

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Immunotherapy has revolutionized the modality for establishing a firm immune response and immunological memory. However, intrinsic limitations of conventional low responsive poor T cell infiltration and immune related adverse effects urge the coupling of cancer nanomedicines with immunotherapy for boosting antitumor response under ultrasound (US) sensitization to mimic dose-limiting toxicities for safe and effective therapy against advanced cancer. US is composed of high-frequency sound waves that mediate targeted spatiotemporal control over release and internalization of the drug. The unconventional US triggered immunogenic nanoengineered arena assists the limited immunogenic dose, limiting toxicities and efficacies. In this Review, we discuss current prospects of enhanced immunotherapy using nanomedicine under US. We highlight how nanotechnology designs and incorporates nanomedicines for the reprogramming of systematic immunity in the tumor microenvironment. We also emphasize the mechanical and biological potential of US, encompassing sonosensitizer activation for enhanced immunotherapeutic efficacies. Finally, the smartly converging combinational platform of US stimulated cancer nanomedicines for amending immunotherapy is summarized. This Review will widen scientists' ability to explore and understand the limiting factors for combating cancer in a precisely customized way.

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Protoporphyrin IX-mediated sonodynamic therapy promotes autophagy in vascular smooth muscle cells

Cited by 9 publications

References 32 publications

Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Inhibits RIP3 Expression and Induces Apoptosis in the H446 Small Cell Lung Cancer Cell Line

Sinoporphyrin Sodium-Mediated Sonodynamic Therapy Inhibits RIP3 Expression and Induces Apoptosis in the H446 Small Cell Lung Cancer Cell Line

Function of Epirubicin-Conjugated Polymeric Micelles in Sonodynamic Therapy

Enhancing Cancer Immunotherapeutic Efficacy with Sonotheranostic Strategies

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